Publications by authors named "Lluís Puig"

152 Publications

Exploring the Role of IL-36 Cytokines as a New Target in Psoriatic Disease.

Int J Mol Sci 2021 Apr 21;22(9). Epub 2021 Apr 21.

Dermatology Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain.

Unmet needs in the treatment of psoriasis call for novel therapeutic strategies. Pustular psoriasis and psoriatic arthritis often represent a therapeutic challenge. Focus on IL-36 cytokines offers an interesting approach, as the IL-36 axis has been appointed a critical driver of the autoinflammatory responses involved in pustular psoriasis. Two IL-36R blocking antibodies, imsidolimab and spesolimab, are currently undergoing phase II and III clinical trials, with promising results.
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http://dx.doi.org/10.3390/ijms22094344DOI Listing
April 2021

Impact of PASI response on work productivity and the effect of risankizumab on indirect costs using machine learning in patients with moderate-to-Severe psoriasis.

J Dermatolog Treat 2021 Apr 25:1-26. Epub 2021 Apr 25.

Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.

Objectives: To compare the impact of Psoriasis Area and Severity Index (PASI) response on total work productivity impairment (TWPI) in patients with moderate-to-severe psoriasis; to compare TWPI and associated indirect costs among patients treated with risankizumab, adalimumab, ustekinumab, and placebo.

Methods: Data from REVEAL (adalimumab phase III trial) were used to assess differences in trial-observed TWPI across PASI response cohorts. A machine learning model used REVEAL data to predict TWPI for patients in the risankizumab trials. These values were used to estimate work loss hours and work impairment-related indirect costs for each treatment cohort.

Results: Among REVEAL patients ( = 741), TWPI in the PASI 100, 90-99, 75-89 cohorts was lower than the PASI <75 cohort ( < 0.05); mean TWPI was lowest with PASI 100 (1.7%) vs. 90-99 (2.5%) vs. 75-89 (4.8%) vs. <75 (14.3%). There was a significant ( < 0.0001) monotonic relationship between higher PASI response and lower TWPI. In the risankizumab trials ( = 2,046), incremental TWPI relative to risankizumab was 3.4%/week for ustekinumab/adalimumab, and 17.1%/week for placebo; incremental indirect cost savings for risankizumab were $2,179/year vs. adalimumab, $2,321/year vs. ustekinumab, and $11,284/year vs. placebo.

Conclusions: Higher PASI responses were associated with reduced TWPI. Risankizumab was associated with less work impairment/indirect costs versus ustekinumab/adalimumab/placebo.
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http://dx.doi.org/10.1080/09546634.2021.1919287DOI Listing
April 2021

Autochthonous and imported tegumentary leishmaniasis in Catalonia (Spain): Aetiological evolution in the last four decades and usefulness of different typing approaches based on biochemical, molecular and proteomic markers.

Transbound Emerg Dis 2021 Apr 17. Epub 2021 Apr 17.

Secció de Parasitologia, Departament de Biologia, Sanitat i Medi Ambient, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Barcelona, Spain.

Leishmaniasis is a transmissible disease caused by Leishmania protozoa. Spain is endemic for both visceral and cutaneous leishmaniasis, the autochthonous aetiological agent being Leishmania infantum. Around the world, the L. donovani complex is associated with visceral symptoms, while any species of the Leishmania or Viannia subgenera affecting human can produce tegumentary forms. In a context of growing numbers of imported cases, associated with globalisation, the aim of this study was to analyse the aetiological evolution of human tegumentary leishmaniasis in a region of Spain (Catalonia). Fifty-six Leishmania strains, isolated from 1981 to 2018, were analysed using MLEE, gene sequencing (hsp70, rpoIILS, fh and ITS2) and MALDI-TOF. The utility of these different analytical methods was compared. The results showed an increase in leishmaniasis over the two last decades, particularly imported cases, which represented 39% of all cases studied. Leishmania infantum, L. major, L. tropica, L. braziliensis, L. guyanensis and L. panamensis were identified. The combination of molecular and enzymatic methods allowed the identification of 29 different strain types (A to AC). Strain diversity was higher in L. (Viannia), whilst the different L. major types were relatable with geo-temporal data. Among the autochthonous cases, type C prevailed throughout the studied period (39%). Minor types generally appeared within a short time interval. While all the techniques provided identical identification at the species complex level, MALDI-TOF and rpoIILS or fh sequencing would be the most suitable identification tools for clinical practice, and the tandem hsp70-ITS2 could substitute MLEE in the epidemiological field.
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http://dx.doi.org/10.1111/tbed.14107DOI Listing
April 2021

SARS-CoV-2/COVID-19 pandemic: first wave, impact, response and lessons learnt in a fully integrated Regional Blood and Tissue Bank. A narrative report.

Blood Transfus 2021 03 15;19(2):158-167. Epub 2021 Jan 15.

Banc de Sang i Teixits (BST), Barcelona, Spain.

Background: The COVID-19 pandemic is placing blood and tissue establishments under unprecedented stress, putting its capacity to provide the adequate care needed at risk. Here we reflect on how our integrated organisational model has faced the first impact of the pandemic and describe what challenges, opportunities and lessons have emerged.

Materials And Methods: The organisational model of the Catalan Blood and Tissue Bank (Banc de Sang i Teixits, BST) is described. The new scenario was managed by following international recommendations and considering the pandemic in a context of volatility, uncertainty, complexity, and ambiguity (VUCA), allowing rapid measures to be taken. These aimed to: ensure donor safety, promote proper responses to patients' needs, ensure the health and well-being of personnel, and prepare for future scenarios.

Results: The BST has adapted its activities to the changes in demand. No shortage of any product or service occurred. Donor acceptance, safety and wellbeing were maintained except for tissue donation, which almost completely stopped. To support the health system, several activities have been promoted: large-scale convalescent plasma (CP) production, clinical trials with CP and mesenchymal stromal cells, massive COVID-19 diagnoses, and participation in co-operative research and publications. Haemovigilance is running smoothly and no adverse effects have been detected among donors or patients.

Discussion: Several elements have proven to be critical when addressing the pandemic scenario: a) the early creation of a crisis committee in combination with technical recommendations and the recognition of a VUCA scenario; b) identification of the strategies described; c) the integrated donor-to-patient organisational model; d) active Research and Development (R&D); and e) the flexibility of the staff. It is essential to underline the importance of the need for centralised management, effective contingency strategies, and early collaboration with peers.
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http://dx.doi.org/10.2450/2021.0259-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925220PMC
March 2021

The interleukin-1 family cytokines in psoriasis: pathogenetic role and therapeutic perspectives.

Expert Rev Clin Immunol 2021 Feb 17;17(2):187-199. Epub 2021 Feb 17.

Department of Dermatology, Hospital De La Santa Creu I Sant Pau, Barcelona, Spain.

: IL-1 family cytokines play an important role in the innate immune system and their uncontrolled activation and expression can initiate a pathologic inflammatory response. Their role in psoriasis, pustular psoriasis, and psoriatic arthritis has been studied, and they offer potential interest as therapeutic targets.: This review focuses on the role that interleukin (IL)-1 family cytokines play in psoriasis pathogenesis, with a special focus on pustular psoriasis, and how these cytokines can be used as therapeutic targets. Using PubMed, we review the literature for articles related to IL-1 family cytokines and psoriasis, focusing on pustular psoriasis, and including pathogenesis, genetics and therapeutic targets.: IL-1 and IL-36 cytokines act as critical drivers of the autoinflammatory responses involved in pustular psoriasis. Studies on the specific role of each IL-1 cytokine are needed, as well as of their regulatory pathways. Targeting of IL-1 family cytokines has been used in pustular psoriasis, with IL-1 and IL-36 R blockade showing promising results.
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http://dx.doi.org/10.1080/1744666X.2021.1886081DOI Listing
February 2021

IL-13 antagonists in the treatment of atopic dermatitis.

Immunotherapy 2021 Mar 12;13(4):327-344. Epub 2021 Jan 12.

Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Mas Casanovas 90, Barcelona 08041, Spain.

Atopic dermatitis (AD) is a prevalent inflammatory skin disease. IL-13 contributes significantly to the pathogenesis of AD in several ways, and beneficial results have been demonstrated with anti-IL-13 therapies. Currently, the only monoclonal antibody (mAb) approved for AD treatment is dupilumab, an antagonist of the IL-4 receptor alpha (IL-4Rα) subunit common to IL-4 and IL-13 receptors, but clinical trials evaluating anti-IL-13 mAbs are providing promising results. The topics of this review will be mAbs targeting IL-13 for the treatment of AD such as dupilumab, tralokinumab and lebrikizumab, small molecules targeting the IL-13 pathway, and a brief explanation of therapies targeting IL-13 for the treatment of other skin diseases.
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http://dx.doi.org/10.2217/imt-2020-0253DOI Listing
March 2021

Intraoperative Bacterial Contamination and Activity of Different Antimicrobial Prophylaxis Regimens in Primary Knee and Hip Replacement.

Antibiotics (Basel) 2020 Dec 27;10(1). Epub 2020 Dec 27.

Department of Medicine, Faculty of Medicine, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.

Surgical antimicrobial prophylaxis (SAP) is important for the prevention of prosthetic joint infections (PJIs) and must be effective against the microorganisms most likely to contaminate the surgical site. Our aim was to compare different SAP regimens (cefazolin, cefuroxime, or vancomycin, alone or combined with gentamicin) in patients undergoing total knee (TKA) and hip (THA) arthroplasty. In this preclinical exploratory analysis, we analyzed the results of intraoperative sample cultures, the ratio of plasma antibiotic levels to the minimum inhibitory concentrations (MICs) for bacteria isolated at the surgical wound and ATCC strains, and serum bactericidal titers (SBT) against the same microorganisms. A total of 132 surgical procedures (68 TKA, 64 THA) in 128 patients were included. Cultures were positive in 57 (43.2%) procedures (mostly for coagulase-negative staphylococci and spp.); the rate was lower in the group of patients receiving combination SAP (adjusted OR 0.475, CI95% 0.229-0.987). The SAP regimens evaluated achieved plasma levels above the MICs in almost all of intraoperative isolates (93/94, 98.9%) and showed bactericidal activity against all of them (SBT range 1:8-1:1024), although SBTs were higher in patients receiving cefazolin and gentamicin-containing regimens. The potential clinical relevance of these findings in the prevention of PJIs remains to be determined.
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http://dx.doi.org/10.3390/antibiotics10010018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823842PMC
December 2020

Therapeutic targeting of the IL-13 pathway in skin inflammation.

Expert Rev Clin Immunol 2021 Jan 14;17(1):15-25. Epub 2020 Dec 14.

Dermatology Department, Hospital De La Santa Creu I Sant Pau, Universitat Autònoma De Barcelona, Barcelona, Spain.

: Atopic dermatitis (AD) is a heterogeneous, chronic, inflammatory skin disease with a non-negligible prevalence at present. Its pathogenesis is complex, but mainly characterized by constitutive T helper type 2 (Th2)-cell activation. Systemic therapies for moderate-to-severe AD can be associated with adverse events that encumber their satisfactory long-term use. Several drugs targeting relevant molecules in the immunopathogenesis of AD have been approved or are under clinical development for the treatment of moderate to severe AD. To elaborate this review, literature searches were performed in PubMed on 29 August 2020.: This narrative literature review is focused on the pivotal role of IL-13 in the immunopathogenesis of AD and other skin diseases.: Dupilumab has demonstrated the central role of IL-13 and IL-4 in the pathogenesis of AD, asthma, and other diseases in the atopic spectrum. In addition, phase III randomized clinical trials (RCTs) evaluating specific blockade of IL-13 with tralokinumab for treatment of AD also demonstrated favorable results, and phase III RCT evaluating lebrikizumab are ongoing. The role of IL-13 in other skin diseases should be further investigated.
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http://dx.doi.org/10.1080/1744666X.2020.1858802DOI Listing
January 2021

An Analysis of Patient-reported Outcomes in IXORA-S: Comparing Ixekizumab and Ustekinumab over 52 Weeks in Moderate-to-severe Psoriasis.

Acta Derm Venereol 2020 Dec 9;100(19):adv00344. Epub 2020 Dec 9.

Department of Dermatology, Hospital de la Santa Creu i Sant Pau, ES-08041 Barcelona, Spain. E-mail:

Patient-reported outcomes are valuable for assessing new psoriasis therapies. This study investigated patient-reported outcomes in patients with moderate-to-severe plaque psoriasis treated with ixekizumab or ustekinumab, dosed according to their respective labels, for 52 weeks (IXORA-S-NCT02561806). Patient-reported outcomes investigated included patient global assessment, pruritus, skin pain, health-related quality of life, and work productivity. Ixekizumab-treated patients reported greater improvements in patient-reported outcomes sooner after treatment compared with ustekinumab-treated patients, and maintained greater improvements in patient global assessment scores (ixekizumab 0.72, ustekinumab 1.19; p < 0.001), rates of Dermatology Life Quality Index (0, 1) (ixekizumab 71.3%, ustekinumab 56.6%, p < 0.01), and 36-item Short-form Health survey physical component summary score change from baseline (ixekizumab 5.53, ustekinumab 3.28; p < 0.05) at week 52. While clinically meaningful improvements in patient-reported outcomes resulted with either treatment, ixekizumab provided more rapid improvements in patient-reported outcomes and superior outcomes for some assessments through one year of treatment, while maintaining statistically superior improvements in skin severity, as assessed by either physicians or patients.
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http://dx.doi.org/10.2340/00015555-3700DOI Listing
December 2020

Occupational allergic contact dermatitis to isobornyl acrylate present in cell phone screen protectors.

Contact Dermatitis 2021 May 8;84(5):352-354. Epub 2020 Dec 8.

Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1111/cod.13747DOI Listing
May 2021

Relationship between the ABO blood group and COVID-19 susceptibility, severity and mortality in two cohorts of patients.

Blood Transfus 2021 01 12;19(1):54-63. Epub 2020 Nov 12.

BST-Barcelona, Central Services, Barcelona, Spain.

Background: Several articles reported the existence of an association between ABO blood groups and COVID-19 susceptibility. Group A and group O individuals showed a higher and lower risk, respectively, of becoming infected. No association was observed between ABO groups and mortality. To verify this association, we performed a retrospective study of two cohorts of patients with different demographic and clinical characteristics.

Material And Methods: A total of 854 regular blood donors were recruited for convalescent plasma donation after recovering from a mild COVID-19 infection, and a group of 965 patients more severely affected who were transfused during hospitalisation were also included. We also investigated the potential role of the different risk factors on patient outcome and death. To eliminate the confounding effect of risk factors on mortality, a propensity score analysis was performed.

Results: Blood group A and blood group O COVID-19 blood donors showed a higher and lower risk, respectively, for acquiring COVID-19. In contrast, this association was not found in the group of patients transfused during hospitalisation, probably due to the great differences in demographic and clinical characteristics between the two groups. Regarding severity, age was one of the most significant risk factors. ABO blood groups were also seen to represent important risk factors for COVID-19 severity and mortality. Mortality risk in group A individuals was significantly higher than in group O individuals (OR: 1.75, 95% CI: 1.22-2.51).

Discussion: The association between the ABO blood groups and the susceptibility to acquire COVID-19 infection was confirmed in the group of blood donors. ABO blood groups were also associated to COVID-19 severity and mortality in the group of patients transfused during hospitalisation. Therefore, blood groups A and O are two important factors to be considered when evaluating the prognosis of patients with COVID-19.
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http://dx.doi.org/10.2450/2020.0256-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850930PMC
January 2021

An atypical and infrequent palmoplantar affection.

Int J Dermatol 2021 Jun 29;60(6):703-704. Epub 2020 Sep 29.

Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1111/ijd.15211DOI Listing
June 2021

Sequential paradoxical psoriasiform reaction and sacroiliitis following adalimumab treatment of hidradenitis suppurativa, successfully treated with guselkumab.

Dermatol Ther 2020 11 13;33(6):e14180. Epub 2020 Sep 13.

Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1111/dth.14180DOI Listing
November 2020

Clinical and genetic evaluation of six children with diffuse capillary malformation and undergrowth.

Pediatr Dermatol 2020 Sep 1;37(5):833-838. Epub 2020 Jul 1.

Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Background: Diffuse capillary malformation with overgrowth (DCMO) has been well described. However, capillary malformation with undergrowth (CMU) has been less reported in the literature.

Objectives: We sought to describe the clinical features and determine associated somatic mutations in patients with CMU.

Methods: We searched our multidisciplinary vascular anomalies clinic database for patients with CMU. Girth and length limb measurements were performed. In case of discrepancies in length, long leg radiograph studies were obtained. Whole-exome sequencing of blood and involved tissue DNA was carried out.

Results: We included six patients with CM and soft-tissue and bone undergrowth. CMs were patchy, reticulated, segmental, poorly demarcated, pink-red stains affecting the lower limb (five patients) or the whole hemibody (one patient). In five patients, the stain was diffuse, affecting more than one anatomic region. Prominent superficial veins were observed in three patients. Five patients presented with lower limb girth discrepancy; in three of them, there was also lower limb length discrepancy. In the remaining patient, only lower limb length discrepancy was found. Whole-exome sequencing from DNA tissue/blood detected previously described pathogenic somatic mutations on DDR2 (c.314G > A; p.Arg105His), GRHL2 (c.791A > G; p.Glu264Gly), and PIK3CA (c.2740G > A; p.Gly914Arg) genes.

Conclusion: We propose the term "diffuse capillary malformation with undergrowth" for extensive reticular CMs associated with proportionate undergrowth. All our patients had a favorable outcome, and no genotype-phenotype association was found.
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http://dx.doi.org/10.1111/pde.14252DOI Listing
September 2020

Propranolol-resistant infantile hemangioma successfully treated with sirolimus.

Pediatr Dermatol 2020 Jul 23;37(4):684-686. Epub 2020 Apr 23.

Department of Dermatology, Hospital Sant Joan de Deu, Barcelona, Spain.

Infantile hemangiomas are the most common benign vascular tumors in childhood. Propranolol is the first-line treatment for infantile hemangiomas, but failures may occur. Sirolimus, an mTOR inhibitor, is a promising drug for the treatment of vascular malformations and vascular tumors. We present the case of a child with multiple infantile hemangiomasthat was successfully treated with sirolimus and propranolol after failure of combined propranolol and prednisolone treatment.
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http://dx.doi.org/10.1111/pde.14163DOI Listing
July 2020

Guselkumab in the treatment of moderate-to-severe plaque psoriasis.

Immunotherapy 2020 04 21;12(6):355-371. Epub 2020 Apr 21.

Department of Dermatology, Hospital de la Santa Creu i Sant Pau. Autonomous University of Barcelona, Mas Casanovas 90. 08041 Barcelona, Catalonia, Spain.

Recent advances in our understanding of the immunopathogenesis of psoriasis have resulted in novel therapeutic agents. IL-23, mainly produced by dendritic cells, maintains the differentiation of naive T cells to Th17 cells, the keystone effector cells in psoriasis. The clinical effectiveness of therapeutic agents targeting this cytokine has been demonstrated in moderate-to-severe plaque psoriasis. Guselkumab is the first human antibody against the p40 subunit of the IL-23 receptor approved by the US FDA and the EMA for this indication in adult patients (2017). It has also been approved for treatment of psoriatic arthritis in Japan (April 2018). This article reviews the published data relating to the efficacy and safety of guselkumab for treatment of moderate-to-severe plaque psoriasis.
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http://dx.doi.org/10.2217/imt-2020-0040DOI Listing
April 2020

Safety of calcipotriene and betamethasone dipropionate foam for the treatment of psoriasis.

Expert Opin Drug Saf 2020 Apr 13;19(4):423-432. Epub 2020 Apr 13.

Department of Dermatology, Hospital De La Santa Creu I Sant Pau. Universitat Autònoma De Barcelona, Barcelona, Catalonia, Spain.

Psoriasis vulgaris is a chronic inflammatory skin disease characterized by well-demarcated red and scaly plaques. Most patients have mild disease that is usually controlled with topical treatment. Calcipotriene 0.05% and betamethasone dipropionate 0.064% (Cal/BD) in aerosol foam (Enstilar®) is a novel formulation, which has shown promising results in terms of efficacy and safety. This review evaluates the safety profile of Cal/BD aerosol foam and also the key points regarding its efficacy. A literature search was performed in PubMed in November 2019 from the start of records. Additional references were searched and retrieved manually. Cal/BD aerosol foam has proven its efficacy, safety, and tolerability in several clinical trials and real clinical practice. It has also demonstrated higher efficacy than the ointment and gel formulations of the fixed combination. It has a low incidence of adverse events; nasopharyngitis and site application pain were the most frequently reported. Moreover, it is devoid of changes in calcium homeostasis and hypothalamic-pituitary-adrenal axis. As a result of its unique formulation, it is easily spread, is rapidly absorbed, and has a rapid onset of action. These features upgrade patient's satisfaction and they may increase adherence to topical therapy.
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http://dx.doi.org/10.1080/14740338.2020.1749594DOI Listing
April 2020

Sonication in shoulder surgery: is it necessary?

Int Orthop 2020 09 26;44(9):1755-1759. Epub 2020 Mar 26.

Department of Orthopedics, Hospital del Mar, Parc de Salut Mar, Passeig Marítim 25-29, 08003, Barcelona, Spain.

Purpose: The objective of the present study was to determine whether sonication yields greater sensitivity when compared with the traditional tissue culture in detecting peri-implant infections in shoulder surgery.

Methods: It is a retrospective study that includes 99 shoulder surgeries with implants explanted. The inclusion criteria required at least four tissue cultures, sonication of the material explanted, and a minimum follow-up of two years. Patients were classified according to the definition of periprosthetic shoulder infection of the 2018 International Consensus Meeting on Orthopedic Infections. The classifications are definitive infection, probable infection, possible infection, and unlikely infection.

Results: Among the 99 surgical procedures, 31 were considered definitive infections, 11 possible/probable infections, and 57 unlikely infections. Considering the cases with a definitive infection, the sensitivity of the tissue culture was 87.09% and the sensitivity of sonication stood at 80.64% (p = 0.406). Analyzing the cases with a definitive infection and those having a possible/probable infection together and comparing them with those with unlikely infection, the sensitivity of sonication was 80.4% and the sensitivity of the tissue culture came to 91.4%. The specificity of the sonication was 98.1% and the specificity of the tissue culture was 99.6%.

Conclusion: The sensitivity of sonication in shoulder surgery (80.64%) is not superior to the sensitivity of the tissue culture (87.09%). Specificity remains high with both methods, being 98.1% in the sonication group and 99.6% in the tissue culture. Sonication brings no benefit to the detection of shoulder per-implant infections.
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http://dx.doi.org/10.1007/s00264-020-04543-8DOI Listing
September 2020

The safety of brodalumab for the treatment of psoriasis.

Expert Opin Drug Saf 2020 Apr 21;19(4):365-372. Epub 2020 Feb 21.

Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.

: Brodalumab is a newly developed targeted biologic agent for the treatment of psoriasis that blocks IL-17 receptor A.: This review sought to provide a detailed overview on safety of brodalumab for the treatment of psoriasis. A PubMed search was conducted for relevant literature. Here we review the efficacy and safety data from key phase II, phase III and open-label extension clinical trials, as well as systematic reviews and meta-analyses.: The unique mechanism of action of brodalumab offers advantages on efficacy over other targeted treatments, with a quick onset of action and long-term maintenance of treatment response. Brodalumab has a favorable safety profile, similar to other IL-17 inhibitors. Infections, especially mucocutaneous candidiasis, must be monitored. Suicidal ideation was detected in brodalumab trials, although a causal relationship has not been revealed. Brodalumab is a highly efficacious and comparably safe therapeutic choice in patients with moderate to severe psoriasis, especially when rapid control of the disease is desired.
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http://dx.doi.org/10.1080/14740338.2020.1730326DOI Listing
April 2020

A Comparison of Psoriasis Severity in Pediatric Patients Treated With Methotrexate vs Biologic Agents.

JAMA Dermatol 2020 04;156(4):384-392

Department of Dermatology, Radboud University, Nijmegen, the Netherlands.

Importance: Few studies have compared the use of methotrexate and biologics, the most commonly used systemic medications for treatment of moderate to severe psoriasis in children.

Objective: To assess the real-world, 6-month reduction in psoriasis severity and long-term drug survival (rate and duration of adherence to a specific drug) of methotrexate vs biologics in plaque psoriasis in children.

Design, Setting, And Participants: A retrospective medical records review was conducted at 20 European and North American centers. Treatment response was based on site-reported Psoriasis Area and Severity Index (PASI) and/or Physician Global Assessment (PGA) scores at baseline and within the first 6 months of treatment. Participants included all 234 consecutively seen children with moderate to severe psoriasis who received at least 3 months of methotrexate or biologics from December 1, 1990, to September 16, 2014, with sufficient data for analysis. Data analysis was performed from December 14, 2015, to September 1, 2016.

Main Outcomes And Measures: PASI, with a range from 0 to 72 (highest score indicating severe psoriasis), and/or PGA, with a scale of 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), and 5 (very severe).

Results: Of 234 pediatric patients (103 boys [44.0%]; 131 girls [56.0%]) treated with methotrexate and/or biologics, 163 patients (69.7%) exclusively received methotrexate, 47 patients (20.1%) exclusively received biologics, and 24 children (10.2%) received methotrexate and biologics sequentially. Of the latter cohort, 23 children were treated initially with methotrexate. Mean (SD) age at initiation was 11.6 (3.7) years for methotrexate and 13.3 (2.9) years for biologics (73.2% for etanercept) (P = .002). Among patients evaluated by a scoring method at 6-month follow-up, 75% or greater improvement in PASI (PASI75) was achieved in 12 of 30 patients (40.0%) receiving methotrexate and 20 of 28 patients (71.4%) receiving biologics, and PGA was clear/almost clear (PGA 0/1) in 41 of 115 patients (35.6%) receiving methotrexate and 18 of 37 patients (48.6%) receiving biologics. Achieving PASI75 and/or PGA 0/1 between baseline and 6 months was more likely with biologics than methotrexate (PASI75: odds ratio [OR], 4.56; 95% CI, 2.02-10.27; P < .001; and PGA 0/1: OR, 2.00; 95% CI, 0.98-4.00; P = .06). Decreased mean PASI and PGA scores were associated with biologics more than with methotrexate (PASI effect, -3.13; 95% CI, -4.33 to -1.94; P < .001; and PGA effect, -0.31; 95% CI, -0.56 to -0.06; P = .02). After 1, 3, and 5 years of use, overall drug survival rates for methotrexate were 77.5%, 50.3%, and 35.9%, and for biologics, the rates were 83.4%, 64.3%, and 57.1%, respectively. Biologics were associated with a better confounder-corrected drug survival than methotrexate (hazard ratio [HR], 2.23; 95% CI, 1.21-4.10; P = .01). Discontinuation owing to lack of response was comparable (HR, 1.64; 95% CI, 0.80-3.36; P = .18).

Conclusions And Relevance: Methotrexate and biologics appear to be associated with improvement in pediatric psoriasis, although biologics seem to be associated with greater reduction in psoriasis severity scores and higher drug survival rates than methotrexate in the real-world setting. Additional studies directly comparing these medications should be performed for confirmation.
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http://dx.doi.org/10.1001/jamadermatol.2019.4835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042803PMC
April 2020

Purple ulcerated nodules in a middle-aged man.

Int J Dermatol 2020 Apr 13;59(4):e96-e98. Epub 2020 Jan 13.

Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1111/ijd.14771DOI Listing
April 2020

The safety of ixekizumab in psoriasis drug therapy.

Authors:
Lluís Puig

Expert Opin Drug Saf 2020 Feb 6;19(2):117-130. Epub 2020 Feb 6.

Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.

: Ixekizumab, a humanized IgG4 monoclonal antibody that selectively binds and neutralizes interleukin IL-17A, has been approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of moderate to severe plaque psoriasis (2016), active psoriatic arthritis (FDA 2017, EMA 2018), and active ankylosing spondylitis (FDA 2019).: This review evaluates the safety profile of ixekizumab for the treatment of moderate-to-severe psoriasis. A literature search was performed for articles published through November 2019.: These studies show that ixekizumab demonstrates a favorable safety profile. Antidrug antibodies can be detected in up to 17% of patients but they do not significantly affect clinical response or safety of the treatment. Injection site reactions, erythema or pain, develop in up to 10% of the patients during the first 12 weeks of treatment, an incidence similar to that of etanercept. Infections overall do not cause a safety problem; mucocutaneous infections, occur at a rate of in 1.9/100 patient-years, but are easily managed and usually do not determine treatment discontinuation. The occasional de novo appearance or exacerbation of preexistent inflammatory bowel disease remains a cause of concern, and requires close monitoring of patients at risk.
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http://dx.doi.org/10.1080/14740338.2020.1709440DOI Listing
February 2020

High Levels of Platelet-Lymphocyte Complexes in Patients with Psoriasis Are Associated with a Better Response to Anti-TNF-α Therapy.

J Invest Dermatol 2020 06 26;140(6):1176-1183. Epub 2019 Nov 26.

Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Electronic address:

Psoriasis is currently considered to be an immune-mediated disease whose patho-mechanisms involve platelet activation, which seems to correlate with the activity of the disease. Platelet activation is associated with the formation of platelet-lymphocyte complexes (PLyC), although their significance remains unknown. Moreover, biological treatments that target tumor necrosis factor-α (TNF-α) reduce platelet activation. To clarify the significance of PLyC, we compared their levels in patients with psoriasis with those of healthy donors and determined whether platelet binding modifies the secretion of IL-17A by T helper cells. Finally, we assessed the effect of anti-TNF-α treatment on PLyC in responder and non-responder patients with psoriasis. Ours results demonstrated an increase in PLyC in patients with psoriasis. Moreover, the percentage of IL-17-secreting cells was observed to be higher in the platelet-lymphocyte complex population, and these cells tended to secrete greater amounts of IL-17A. Psoriasis patients treated with anti-TNF-α normalized platelet-lymphocyte complex values, and the basal percentage of platelet-T helper lymphocyte complexes was significantly higher in the responder group. In conclusion, PLyC are increased in psoriasis patients, and the number of complexes decreases in response to anti-TNF-α treatment, specifically in the responder group of patients. This finding suggests that PLyC are a prognostic biomarker of response to anti-TNF-α therapy, but prospective studies are necessary to verify these results in patients with psoriasis.
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http://dx.doi.org/10.1016/j.jid.2019.08.457DOI Listing
June 2020

Psoriasis and Mental Health Workshop Report: Exploring the Links between Psychosocial Factors, Psoriasis, Neuroinflammation and Cardiovascular Disease Risk.

Acta Derm Venereol 2020 01 7;100(1):adv00020. Epub 2020 Jan 7.

Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.

Psoriasis is a systemic, relapsing, inflammatory disease associated with serious comorbidities including mood problems and/or unhealthy lifestyle behaviours. Cutaneous and systemic abnormalities in innate and acquired immunity play a role in its pathogenesis. The exact pathogenetic mechanism remains elusive. Evidence is accumulating that TNF-alpha, IL-17 and IL-23 signalling are highly relevant as targeting these pathways reduces disease activity. Evidence suggests a strong link between psoriasis and depression in adults. The International Psoriasis Council (IPC) held a roundtable event, "Psoriasis and Mental Health", in Barcelona, Spain which focused on the presence of depression and suicidality, plus the role of neuroinflammation in psoriasis, sleep disruption and the impact of depression on cardiovascular disease outcomes. We summarize here the expert presentations to provide additional insight into the understanding of psychiatric comorbidities of psoriasis and of the impact of chronic, systemic inflammation on neuro- and cardiovascular outcomes. the associations between psoriasis and other psychiatric comorbidities are still controversial and warrant further attention.
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http://dx.doi.org/10.2340/00015555-3375DOI Listing
January 2020

Critical role of interleukin (IL)-17 in inflammatory and immune disorders: An updated review of the evidence focusing in controversies.

Autoimmun Rev 2020 Jan 15;19(1):102429. Epub 2019 Nov 15.

Rheumatology División, IDIVAL, Hospital Universitario Marqués de Valdecilla, Santander, Spain; University of Cantabria, Santander, Spain.

Interleukin 17 (IL-17) is a proinflammatory cytokine that has been the focus of intensive research because of its crucial role in the pathogenesis of different diseases across many medical specialties. In this context, the present review in which a panel of 13 experts in immunology, dermatology, rheumatology, neurology, hematology, infectious diseases, hepatology, cardiology, ophthalmology and oncology have been involved, puts in common the mechanisms through which IL-17 is considered a molecular target for the development of novel biological therapies in these different fields. A comprehensive review of the literature and analysis of the most outstanding evidence have provided the basis for discussing the most relevant data related to IL-17A blocking agents for the treatment of different disorders, such as psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, cardiovascular disorders, non alcoholic fatty liver disease, multiple sclerosis, inflammatory bowel disease, uveitis, hematological and solid cancer. Current controversies are presented giving an opening line for future research.
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http://dx.doi.org/10.1016/j.autrev.2019.102429DOI Listing
January 2020

Biosimilars for the treatment of psoriasis.

Expert Opin Biol Ther 2019 10 1;19(10):993-1000. Epub 2019 Jul 1.

Department of Dermatology, Hospital de la Santa Creu i Sant Pau , Barcelona , Spain.

: Biosimilars are biological products that are very similar to their originators, with no meaningful differences in terms of efficacy, safety, and purity. Since the patents of some of the biologics used to treat patients with psoriasis have expired, uptake of biosimilars provides a good opportunity to reduce the cost of treatment. : In this review we summarize the stages in development of a biosimilar product, the main differences with the originator biologic, and their potential implications. We have also reviewed clinical trials of biosimilars approved for the treatment of psoriasis. : Because of efficacy and convenience of administration, adalimumab biosimilars will be used to greater extent than etanercept or infliximab to treat patients with moderate-to-severe psoriasis. The pharmacokinetics, efficacy, safety and immunogenicity of approved biosimilars are equivalent to those of their reference products in clinical trials, and multiple-switch studies are intended to provide evidence in support of FDA-required interchangeability. Non-medical switching is expected to become frequent, and the nocebo effect will be relevant. Traceability of biologics is an essential requirement to gather relevant information on their long-term efficacy and safety, especially when multiple switches occur.
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http://dx.doi.org/10.1080/14712598.2019.1636963DOI Listing
October 2019

Economic Impact of Etanercept in Patients with Psoriasis and Psoriatic Arthritis in Spain: A Systematic Review.

Dermatol Ther (Heidelb) 2019 Sep 6;9(3):479-496. Epub 2019 May 6.

Pfizer S.L.U., Alcobendas, Madrid, Spain.

Introduction: Etanercept (ETN), a highly effective biological agent for the treatment of psoriasis (PSO) and psoriatic arthritis (PsA), is widely used in Spain. However, evidence of its economic impact is limited, indicating the need for a systematic review of the economic assessments conducted on the use of ETN in the treatment of both PSO and PsA in Spain.

Methods: A systematic review was carried out in PubMed, Embase, Cochrane Library, Health Technology Assessment reports and not indexed sources up to November 2018. The inclusion criteria were economic evaluations (total and partial) and dose optimization studies published in English or Spanish on the use of ETN to treat PSO and PsA for ETN in Spain.

Results: A total of 402 publications were identified, of which 32 were selected for inclusion in the review; of these 32 publications, 81.3% analyzed PSO (14 full economic evaluations, 5 partial economic evaluations and 7 dose optimization studies) and 18.8% analyzed PsA (1 economic analysis and 5 dose optimization studies). The perspective of the Spanish National Health Service (NHS) was used in 90.0% (n = 18) of the full and partial economic evaluations. The time horizons ranged from 12 weeks to 2 years. Reductions in the Psoriasis Area and Severity Index (PASI) of 50, 75 and 90% (PASI 50, 75 and 90, respectively) were most commonly used as efficacy outcomes in the complete evaluations. The economic impact of ETN ranged from €9110-14,337/PASI 75 at 12 weeks (50 mg/week) to €82,279/PASI 90 at 2 years, depending on the health outcome, time horizon and ETN dose used. Only one study determined the cost of using ETN for the treatment of PSO (€29,430-52,367/QALY for dose 2 × 25 mg/week or 50 mg/week, respectively). Only one partial economic evaluation on PSA was identified (NHS perspective), resulting in an ETN annual cost of €8585/patient-year.

Conclusion: Consistent evidence on the economic impact of ETN for the treatment of PSO and PSA in Spain is lacking, mainly due to the highly heterogeneous methodology used and the broad range of outcomes found in the economic evaluations published to date.

Funding: Pfizer S.L.U.
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http://dx.doi.org/10.1007/s13555-019-0301-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704195PMC
September 2019

Association Between Enthesitis and Health-related Quality of Life in Psoriatic Arthritis in Biologic-naive Patients from 2 Phase III Ustekinumab Trials.

J Rheumatol 2019 11 1;46(11):1458-1461. Epub 2019 Apr 1.

From the University of Glasgow, Institute of Infection Immunity and Inflammation, Glasgow Biomedical Research Centre, Glasgow, Scotland; Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York; University of Rochester, Medical Center, Rochester, New York; Janssen Research & Development LLC, Spring House, Pennsylvania; Janssen Scientific Affairs LLC, Horsham, Pennsylvania, USA; Memorial University, St. John's, Newfoundland and Labrador, Canada; University of California-San Diego, San Diego, California, USA.

Objective: Evaluate enthesitis, physical function, and health-related quality of life (HRQOL) among patients with psoriatic arthritis (PsA) who are naive to anti-tumor necrosis factor agents.

Methods: In PSUMMIT 1 and 2, patients with PsA were randomized to placebo or ustekinumab 45 mg or 90 mg. Enthesitis was assessed at weeks 0 and 24 (Maastricht Ankylosing Spondylitis Enthesitis Score). Assessments included Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study Short Form-36 (SF-36) physical component summary/mental component summary (PCS/MCS), and American College of Rheumatology 20 (ACR20).

Results: At Week 24, 21 had worsened enthesitis, 158 had improved enthesitis, and 412 had unchanged enthesitis. Improved enthesitis was associated with improvements in HAQ-DI and SF-36 MCS. Results were similar for ACR20 responders and nonresponders.

Conclusion: Improvement in enthesitis at Week 24 was associated with improvements in physical function/HRQOL regardless of ACR20 response.
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http://dx.doi.org/10.3899/jrheum.180792DOI Listing
November 2019